Revisiting the absolute chirality and polymorphism of (–)-Istanbulin A

Abstract

The terpenoid (−)-Istanbulin A is a natural product isolated from Senecio filaginoides DC, one of the 270 species of Senecio (Asteraceae) which occurs in Argentina. The structure and absolute configuration of this compound [9a-hydroxy-3,4a,5-trimethyl-4a,6,7,8a,9,9a-hexahydro-4H,5H-naphtho[2,3-b]-furan-2,8-dione or (4S,5R,8R,10S)-1-oxo-8β-hydroxy-10βH-eremophil-7(11)-en-12,8β-olide, C15H20O4] were determined by single-crystal X-ray diffraction studies. It proved to be a sesquiterpene lactone showing an eremophilanolide skeleton whose chirality is described as 4S,5R,8R,10S. Structural results were also in agreement with the one- and two-dimensional (1D and 2D) NMR and HR–ESI–MS data, and other complementary spectroscopic information. In addition, (−)-Istanbulin A is a polymorph of the previously reported form of (−)-Istanbulin A, form I; thus, the title compound is denoted form II or polymorph II. Structural data and a literature search allowed the chirality of Istanbulin A to be revisited. The antimicrobial and antifungal activities of (−)-Istanbulin A, form II, were evaluated in order to establish a reference for future comparisons and applications related to specific crystal forms of Istanbulins.

Using DP4+ probability for structure elucidation of sesquiterpenic lactones: The case of (−)‐Istanbulin A

“…In this sense, (−)‐Istanbulin A emerges as a promising antibacterial and antifungal compound. [ 6,7 ]…”

“…The molecular structure of (−)‐Istanbulin A has been recently studied by means of X‐ray diffraction, 1 HNMR, and 13 CNMR. [ 6,8 ] Its absolute configuration was determined by means of Flack, Hooft y , and P2(true) parameters, [ 9,10 ] thus proposing for this compound the systematic names (4S,5R,8R,10S)‐1‐oxo‐8‐hydroxy‐10H‐eremophil‐7(11)‐en‐12,8‐olide and (4S,5R,8R,10S)‐9a‐hydroxy‐3,4a,5‐trimethyl‐4a,6,7,8a,9,9a‐hexahydro‐4H,5H‐naphtho[2,3‐b]‐furan‐2,8‐dione. Figure 1 shows the structure proposed in literature, consisting of two 6‐membered rings trans fused (which adopt distorted chair conformations) attached to a quasi‐planar γ‐lactone ring.…”